The identification of saturable, high affinity, and stereospecific binding sites for benzodiazepines has been described in the mammalian central nervous system. The correlations between the binding of a series of benzodiazepines in vitro and their pharmacologic potencies as anxiolytics, anticonvulsants, and muscle relaxants in vivo, strongly suggest these sites are receptors mediating the therapeutic actions of the benzodiazepines. The physiologic role(s) of the benzodiazepine receptor and the pharmacologic, behavioral, and physiologic regulation of this receptor are being investigated using several experimental paradigms, including: 1) the isolation and identification and pharmacologic assessment of endogenous substrates which subserve this receptor (see Project N. Z01 MH 01834-02); 2) development of suitable in vitro models for studying the benzodiazepine receptor such as primary and transformed cultures of neural origin and mammalian retina; 3) development of novel benzodiazepines to characterize receptor subgroups and to determine the physiologic function of these subgroups; 4) development of an irreversible ligand to the benzodiazepine receptor for studying receptor turnover; 5) development of suitable techniques for studying benzodiazepine receptors in vivo.